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A genome-wide association study and several replication studies have shown significant association between BTBD9 gene single nucleotide polymorphisms and restless legs syndrome (RLS). The aim of this study is to investigate the association between the BTBD9 gene polymorphisms and antipsychotic-induced RLS in schizophrenic patients.Restless legs syndrome symptoms were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group in 190 Korean schizophrenic patients. We genotyped the rs9357271 and rs3923809 polymorphisms of the BTBD9 gene in schizophrenic patients with (n = 96) and without (n = 94) RLS symptoms.There was a significant difference in the allele frequency (χ(2) = 8.14, p = 0.004) of the rs9357271 polymorphism between schizophrenic patients with and without RLS symptoms. Significant genotypic association of this single nucleotide polymorphisms with RLS symptoms was also observed for the dominant model (χ(2) = 10.32, p = 0.001) and heterozygous model (χ(2) = 10.9, p = 0.001). When we compared the frequencies of the rs3923809-rs9357271 haplotypes between the two groups, the overall haplotype frequencies were significantly different (permuted p = 0.037), and the A-T haplotype was significantly more frequent in the RLS symptom group than in the no RLS symptom group (0.112 vs. 0.041, permuted p = 0.007).These data suggest that the BTBD9 gene is associated with antipsychotic-induced RLS symptoms in schizophrenic patients.

The aim of this study was to examine disturbances in regional cerebral blood flow (rCBF) associated with methamphetamine abuse.Using Single Photon Emission Computed Tomography (SPECT), rCBF was measured in 20 men who had previously injected methamphetamine intravenously for over 30 months and who were now abstinent for a minimum of 9 months and for an average of 2 years. Values were compared with those in 12 healthy men who had never injected methamphetamine.While rCBF was significantly and disproportionately reduced in subcortical and dorsal cortical brain regions, including the striatum, thalamus, cingulum, mesiodorsal prefrontal cortex, and pons (all t's8.3 after global normalization, corrected p's0.001), whole brain CBF was also significantly reduced in the former methamphetamine users. Binge use of methamphetamine is associated with long-term changes in both global and regional blood flows, likely representing severe and enduring neural toxicity of monoaminergic neurotransmitter systems in the brain, producing a pattern of hypoperfusion that resembles patterns reported previously for persons with atypical Parkinson's disease.These findings suggest that methamphetamine abusers may be possibly at increased risk for neurodegenerative diseases later in life.

Lung cancer is the leading cause of cancer deaths in the United States. In addition to genetic abnormalities induced by cigarette smoke, several epidemiologic studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lungs, have an increased risk of lung cancer (1.3- to 4.9-fold) compared to smokers without COPD. This suggests a link between chronic airway inflammation and lung carcinogenesis, independent of tobacco smoke exposure. We studied this association by assaying the inflammatory impact of products of nontypeable Haemophilus influenzae, which colonizes the airways of patients with COPD, on lung cancer promotion in mice with an activated K-ras mutation in their airway epithelium. Two new mouse models of lung cancer were generated by crossing mice harboring the LSL-K-ras(G12D) allele with mice containing Cre recombinase inserted into the Clara cell secretory protein (CCSP) locus, with or without the neomycin cassette excised (CCSP(Cre) and CCSP(Cre-Neo), respectively). Lung lesions in CCSP(Cre-Neo)/LSL-K-ras(G12D) and CCSP(Cre)/LSL-K-ras(G12D) mice appeared at 4 and 1 month of age, respectively, and were classified as epithelial hyperplasia of the bronchioles, adenoma, and adenocarcinoma. Weekly exposure of CCSP(Cre)/LSL-K-ras(G12D) mice to aerosolized nontypeable Haemophilus influenzae lysate from age 6-14 weeks resulted in neutrophil/macrophage/CD8 T-cell-associated COPD-like airway inflammation, a 3.2-fold increase in lung surface tumor number (156 +/- 9 versus 45 +/- 7), and an increase in total lung tumor burden. We conclude that COPD-like airway inflammation promotes lung carcinogenesis in a background of a G12D-activated K-ras allele in airway secretory cells.

Background Methamphetamine, a derivative of amphetamine, has been well known to cause mental problems in humans; however, its physical effects are little known. Despite relevant information on the effect of methamphetamine abuse on bone quality being available, data regarding the frequency of osteoporosis in methamphetamine abusers are limited. Methods We selected 46 hospitalized male methamphetamine abusers and 188 reference male controls in whom any conditions affecting bone metabolism were ruled out. Bone mineral density (BMD) in the lumbar spine was measured by dual energy X-ray absorptiometry (DXA). We compared the BMD between methamphetamine abusers and controls and evaluated the frequency of osteoporosis in both groups. Results The mean BMD value was lower in methamphetamine abusers (mean±SD, 0.71±0.07g/cm 2 ) than in the controls (mean±SD, 0.98±0.14g/cm 2 ). The frequency of osteoporosis was 22% according to WHO diagnostic guidelines, and osteopenia at the lumbar spine was 76%. The correlation between the extent of methamphetamine abuse and BMD was very clear. Conclusion There was considerable loss of bone mineral in a high percentage of methamphetamine abusers. Our study is the first clinical study to determine the frequency of osteoporosis in male methamphetamine abusers.

Clara cells are nonciliated secretory cells lining the respiratory epithelium and are easily identified by the expression of Clara cell secretory protein (CCSP). To investigate molecular mechanism(s) regulating Clara cell function in the lungs, Cre recombinase was inserted into exon 1 of the CCSP, generating two novel mouse models, CCSP(Cre-Neo) and CCSP(Cre). These two models differ only by the inclusion of the neomycin resistance gene. These mice were bred to the R26R reporter mouse to investigate the tissue and cell specificity of Cre-mediated recombination. The efficiency of Cre recombination in the CCSP(Cre) mouse model was higher than in the CCSP(Cre-Neo) mouse model. Recombination was detected at D 4.5 in CCSP(Cre-Neo)/R26R mice and at D 0.5 in CCSP(Cre)/R26R mice. The CCSP(Cre-Neo) and CCSP(Cre) mouse models provide valuable tools for the ablation of genes in the postnatal mouse Clara cells.

LKB1 is frequently dysregulated in human lung cancer and has been shown to be one of the critical genes controlling the development of lung squamous cell carcinoma (SCC) in mice1,2. However, it's unclear that the contribution of LKB1 in the development of lung SCC in mice. Here we took advantage of our new enhanced Cre (CCSPiCre) to efficiently deplete Lkb1 in the mouse airway epithelial cells. Although ablation of Lkb1 failed to show any discernable morphological changes, microarray analysis revealed 503 genes and 202 LincRNAs were significantly altered after single ablation of Lkb1. Ingenuity Pathway Analysis (IPA) showed that LXR/RXR activation and inflammatory pathways were significantly dysregulated by ablation of Lkb1. Using the CCSPiCre mouse, we ablated Pten in addition to Lkb1. As previously reported by Xu and coworkers who used Adenoviral delivery of Cre recombinase to achieve Lkb1 and Pten ablation2, the resulting phenotype was SCC while much rapider tumor initiation age, higher mouse metastasis ratio and a worse mortality were observed in this efficient mouse model. Analysis of the tumor development showed progression from mucous cell hyperplasia of the large airways to a papillary transition stage, then to the SCC phenotype. Mice with airway specific loss of Lkb1 and only one allele of Pten (CCSPiCrePtenf/+Lkb1f/f) showed slower tumor progression with the strong metastasis ability to multiple organs, such as liver, uterus, intestine and spleen. Comparison of the microarrays of CCSPiCrePtenf/f and CCSPiCrePtenf/fLkb1f/f in the pretumor stage showed 1463 genes and 339 LincRNAs were significantly altered. Again the major altered pathways were inflammatory and cholesterol biosynthesis. Using this model the developmental progression of lung SCC and the contribution of LKB1 to lung SCC progression were determined. References 1. Ji, H., et al. LKB1 modulates lung cancer differentiation and metastasis. Nature 448, 807-810 (2007). 2. Xu, C., et al. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer cell 25, 590-604 (2014). Citation Format: Jian Liu, Sung-Nam Cho, Yiqun Zhang, Chad J. Creighton, Francesco J. DeMayo. The role of LKB1 in development of lung squamous cell carcinoma in mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2308. doi:10.1158/1538-7445.AM2015-2308

Objective The cause of restless legs syndrome (RLS) has not yet been ascertained, but one of the most promising theories involves dopaminergic deficiency. In accordance with this theory, we assumed that the prevalence of RLS would be higher among schizophrenics treated with antipsychotics than in the normal population. The purpose of this study was to establish the prevalence, characteristics, and clinical correlates of RLS in schizophrenic patients undergoing treatment with antipsychotics. Methods A total of 182 hospitalized schizophrenic patients and 108 age- and sex-matched normal controls were enrolled. The presence of RLS and its severity were assessed using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria and the IRLSSG rating scale, respectively. The Athens Insomnia Scale (AIS), Brief Psychiatric Rating Scale (BPRS), and Barnes Akathisia Rating Scale (BARS) were used to evaluate insomnia, global psychiatric symptoms, and akathisia, respectively, in schizophrenic patients. Results Of the 182 schizophrenic patients, 39 (21.4%) were found to have RLS and 87 (47.8%) met at least one of the RLS diagnostic criteria. The prevalence of RLS was significantly higher in the schizophrenia group than in the control group (p = 0.009), as were the RLS scores (p

Major depressive disorder and alcohol dependence are common and serious mental illnesses. There is a great interest in discovering useful treatments for both mood symptoms and alcohol abuse in those patients with depressive disorders and comorbid alcohol dependence. The primary purpose of this study was to evaluate the effectiveness and tolerability of mirtazapine for the treatment of patients with alcohol dependence comorbid with a depressive disorder in an open label, naturalistic multicentre treatment setting. The 17-item Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS) and the Clinical Global Impression-Severity (CGI-S) scale were measured at baseline and at weeks 4 and 8 for the assessment of treatment effectiveness. Alcohol craving was measured using the Obsessive Compulsive Drinking Scale (OCDS) and the Visual Analog Scale for Craving (VAS). This study showed a statistically significant reduction of the scores on the HDRS (13.9+/-7.3, p

Background The aim of the current study was to explore changes of relative regional cerebral blood flow (rCBF) in short-term and long-term abstinent methamphetamine (MA) users. Methods Relative rCBF in 40 abstinent MA users and 23 healthy comparison subjects was compared by the technetium-99m-hexamethyl-propylene amine oxime ( 99m Tc-HMPAO) single photon emission computed tomography (SPECT). Relative rCBF in areas that were found to differ significantly was also compared in groups of MA users with short-term ( Results MA users showed decreased relative rCBF in the right anterior cingulate cortex (Brodmann area 32) relative to healthy comparison subjects. Long-term abstinent MA users had significantly greater rCBF than short-term abstinent MA users. Conclusions We report that abstinent MA users have decreased rCBF in the anterior cingulate cortex with smaller relative decreases in subjects with prolonged abstinence.

Persistent endometriosis after total hysterectomy and both salpingo-oophorectomy (TH with BSO) is a rare condition and the etiology is uncertain. The exact incidence of persistent endometriosis after definitive surgery is not known. In addition, the treatment of persistent endometriosis after complete surgical excision is controversial. We report a case of persistent endometriosis with vaginal and sigmoid-colonic invasion after TH with BSO. The lesions were not responsive to hormonal therapy. The patient was managed successfully by therapeutic pelvic radiation.

Introduction: Lung cancer is the leading cause of cancer death in the world and the incidence of pulmonary adenocarcinoma, the most common type of lung cancer in the United States has been increasing in recent years. Mouse models have played a crucial role in understanding the tumor biology and progression of disease. The need for more clinically relevant preclinical mouse models for lung cancer is clear. Most mouse models for lung cancer use adenoviral delivery or cre recombinase models that result in development of cancers of the distal air ways. The tumors resulting from these mouse models are usually a mixed phenotype with mice developing adenocarcinoma, squamous cell carcinoma and benign adenomas depending on the combination of genetic alterations. We wanted to study lung cancer in the setting of more efficient cre that is present in the proximal as well as the distal lung epithelium. Utilizing this cre-system, we created a double knockout murine model with conditional ablation of pten and smad4 genes and wanted to compare tumor development and progression in these mice when compared to wildtype or smad 4 d/d or pten d/d mice. Methods: All mice were maintained at our core facility under approved protocols. The efficient cre system was accomplished by inserting the iCre recombinase into the Clara Cell Secretory protein locus. Tissues were collected at the time of sacrifice and compared to wild-type mice. Methods include Microarray analysis, RT-PCR, Immunohistochemistry and CHIP-Seq. Results: When compared with wildtype mice, smad 4 d/d or pten d/d alone mice, we have recognized that this particular mouse model has reproducibly developed proximal lung cancers that stain negative for SPC, a marker for distal airways. Additionally, this mouse model has developed metastatic disease, with metastasis to stomach. The immunohistochemistry results confirmed that the metastasis site was positive for TTF-1. Immunohistochemistry for EMT makers show that there is gradual loss of E-Cadherin. Conclusions: We have successfully created a mouse model with CCSPicre/Pten/Smad4 that results in proximal lung tumor development that advances to metastatic disease. Previous studies showed that tissue specific knockout of Smad 4 results in malignancy including gastric polyposis, pancreatic cancer, mammary gland epithelial hyperproliferation and SCC of the skin. Our results add to the previous findings in that loss of Smad4 in conjunction Pten may provide a novel platform to study lung cancer especially as it relates to proximal lung cancers that metastasize. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2346. doi:1538-7445.AM2012-2346

Placenta increta is a condition characterized by abnormal adherence of the placenta owing to entire or partial absence of the decidua basalis. It is generally recognized during difficult placental removal at the time of delivery. It is a life-threatening complication of pregnancy due to massive hemorrhage, uterine perforation, and infection and thus often a hysterectomy is required. We review two cases of placenta increta conservative managed successfully by selective uterine artery embolization.

We demonstrate a novel synthetic scheme that can be used to differentially guide the shape of PbS semiconductor nanocrystals. Our study first demonstrates the discovery of single-crystalline star-shaped nanocrystals as novel transient species. We then carefully probe their shape evolution toward other novel nanostructures (e.g., tadpole-, L-, T-, cross-shapes, highly faceted star shapes, truncated octahedrons and cubes, etc.) and systematically elucidate the key parameters that control these final structures. In principle, through programming these growth parameters, the desired architecture of building blocks of other kinds of nano materials can be constructed.

Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) action. A bias toward E2 action and away from P4 action underlies the tumorigenesis of endometrial adenocarcinoma which is the fourth most common cancer in women. In previous studies, we have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of PR (progesterone receptor) action in the uterus. Mig-6 is expressed in both the epithelium and stroma of the uterus. Conditional ablation of Mig-6 in all compartments of the uterus (PRcre/+ Mig-6f/f) results in infertility and leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. Our central hypothesis is that Mig-6 is a critical mediator of stromal-epithelial communication in pregnancy, steroid hormone regulation and tumor suppressor function. In order to understand the role of epithelial Mig-6 in the uterus, we generated a mouse model in which we specifically ablate epithelial endometrial Mig-6 using Wnt7a-cre mice (Wnt7acre+ Mig-6f/f). Wnt7acre+ Mig-6f/f mice are subfertile due to embryo abortion and display normal P4 attenuation of E2-mediated uterine hypertrophy. However, Wnt7acre+ Mig-6f/f mice develop endometrial hyperplasia at 5 months of age as well as estrogen-induced endometrial cancer. The expression of PR is reduced in Wnt7acre+ Mig-6f/f mice compared to control Mig-6f/f mice. Interestingly, the hyperplasia exhibited by the Wnt7acre+ Mig-6f/f mice is reversed by P4 treatment, contrary to what is observed in PRcre/+ Mig-6f/f mice. Also, the expression of ERα, as well as its target genes Muc-1, Clca3, Ltf and Birc1, is significantly decreased in the Wnt7acre+ Mig-6f/f mice as compared to the control and PRcre/+ Mig-6f/f after P4 treatment. Concurrently, stromal Mig-6 expression is significantly increased in Wnt7acre+ Mig-6f/f mice indicating that P4-induced stromal Mig-6 can reverse the hyperplasia seen in the Wnt7acre+ Mig-6f/f mice by regulating ERα expression level. These data suggest that epithelial Mig-6 plays an important tumor suppressor role during tumorigenesis in the uterus. (Supported by NIH, R01 HD057873) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2197. doi:10.1158/1538-7445.AM2011-2197

To understand a major effect on efficiency droop, radiative characteristics of InGaN laser diodes (LDs) of emission wavelength of ∼445 nm are studied at subthreshold levels for different active structures; (1) InGaN single quantum well (SQW), (2) double quantum wells (DQWs) with Si-doped barrier, and (3) DQWs with undoped barrier. For InGaN LDs with DQWs, the absolute radiative efficiency is most dominant for the case of undoped barrier, and least for the case of Si-doped barrier. The efficiency droop in InGaN LDs with DQWs, regardless of the doping condition of barriers, is typical of reported InGaN light emitting devices, whereas for the InGaN LD with SQW, the efficiency droop is significantly improved for all current density levels due to the least polarization field of InGaN QW.

Adenomyosis is a common gynecological disorder defined by the presence of endometrial glands and stroma within the myometrium. Despite its frequent occurrence, the precise etiology of adenomyosis is still unknown, although it has often been associated with endometrioid adenocarcinoma. β-catenin abnormalities are common in endometrioid type endometrial carcinomas. The expression of the dominant stabilized β-catenin in the murine uterus (PRcre/+ Ctnnb1f(ex3)/+) resulted in endometrial glandular hyperplasia. In addition to the glandular hyperplasia phenotype, uteri of PRcre/+ Ctnnb1f(ex3)/+ mice exhibited an abnormal myometrial structure and proceed to develop adenomyosis. Ablation of Mig-6 in the murine uterus (PRcre/+ Mig-6f/f) leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. Concomitant stabilization of β -catenin and ablation of Mig-6 dramatically accelerated the development of adenomyosis and glandular hyperplasia compared to stablizing β-catenin alone. The adenomyosis phenotype of ovariectomized Pffre/+ Ctnnb1f Citation Information: Clin Cancer Res 2010;16(14 Suppl):B23.

A total of 573 patients hospitalized in National Seoul Mental Hospital and 76 of healthy persons as control were examined by indirect latex agglutination test in order to evaluate Toxoplasma antibody titers in mental patients. Throughout this survey, 1:32 or more titers of diluted sera were regarded as positive. The 573 samples of test sera showed negative in 386 cases (67.4 %), 1:2 in 93 cases (16.2 %), 1:4 in 57 cases (9.9 %), 1:8 in 14 cases (2.4 %), 1:16 in 12 cases (2.1 %), 1:32 in 5 cases (0.9 %), 1:64 in 1 case (0.2 %), 1:128 in 3 cases (0.5 %) and 1:256 in 2 cases (0.3 %) respectively. Among total 573 mental patients, 11 cases (19 %) showed positive, and they were 9 cases (1.8 %) of schizophrenia and 2 cases (7.4 %) of manic depression. One case (1.3 %) out of 76 control sera showed positive result.